Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

Abstract

OBJECTIVES:A 2007 systematic review compared angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in patients with hypertension. Direct renin inhibitors (DRIs) have since been introduced, and significant new research has been published. We sought to update and expand the 2007 review. DATA SOURCES: We searched MEDLINE and EMBASE (through December 2010) and selected other sources for relevant English-language trials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies that directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of follow-up; and reported at least one outcome of interest. Ninety-seven (97) studies (36 new since 2007) directly comparing ACE inhibitors versus ARBs and three studies directly comparing DRIs to ACE inhibitor inhibitors or ARBs were included. STUDY APPRAISAL AND SYNTHESIS METHODS: A standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence. RESULTS: In spite of substantial new evidence, none of the conclusions from the 2007 review changed. The level of evidence remains high for equivalence between ACE inhibitors and ARBs for blood pressure lowering and use as single antihypertensive agents, as well as for superiority of ARBs for short-term adverse events (primarily cough). However, the new evidence was insufficient on long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, and differences in key patient subgroups. LIMITATIONS: Included studies were limited by followup duration, protocol heterogeneity, and infrequent reporting on patient subgroups. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS:Evidence does not support a meaningful difference between ACE inhibitors and ARBs for any outcome except medication side effects. Few, if any, of the questions that were not answered in the 2007 report have been addressed by the 36 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly. CLINICAL CASEA 54-year-old woman with a history of hypertension is seen by her doctor for persistently elevated blood pressure in spite of adherence to hydrochlorothiazide 25 mg daily. She is overweight and has a strong family history of coronary artery disease. To control her blood pressure, she and her doctor discuss adding an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), or a direct renin inhibitor (DRI) to her regimen. She is primarily interested in avoiding the cardiovascular complications of hypertension, but does not want to take medication more than once a day, and she is concerned about side effects and the cost of her medication. What information is available to help guide her decision?Electronic supplementary material The online version of this article

Tolerability of Antihypertensive Medications in Older Adults

“…The role of aldosterone blockade through spironolactone, a mineralocorticoid antagonist, has potential benefit in some cases of resistant hypertension; the main adverse effect of spironolactone use is hyperkalemia [70]. Overall, little difference exists between the classes of ACEIs and ARBs in lowering BP and outcomes, with the exception of ADEs [71]; therefore, factors other than hypertension, such as ADEs, tolerability, and economic factors influence the choice of class. A Cochrane Hypertension Group Specialized Database in conjunction with other sources demonstrated little difference between ACEIs and ARBs regarding mortality and cardiovascular events; but good evidence suggested a lower incidence of withdrawal-related adverse effects for ARBs than for ACEIs.…”

RAS-Mediated Adaptive Mechanisms in Cardiovascular Tissues: Confounding Factors of RAS Blockade Therapy and Alternative Approaches

“…However, according to European Medicines Agency recommendations, aliskiren should not be prescribed to diabetic patients in combination with ACEi or ARBs [40]. The long-term, randomized, placebo-controlled morbidity/mortality trial ALTITUDE, which included 8,600 patients with type 2 diabetes, proteinuria, and a high cardiovascular risk already treated with an ACEi or ARB, was terminated in December 2011 due to an increased incidence of serious adverse events in the aliskiren 300 mg arm [15,16,17,40]. In this context, it is pertinent that chronic suppression of renin does not protect against the profibrotic influence of a chronically elevated urine flow.…”

“…Efficient RAS blockers at all these levels have been developed and are currently in use to block overactivation of RAS and to offer protection from RAS-related metabolic diseases including diabetes [8,9,10,11,12,13]. However, evidence of increased adverse effects from randomized clinical trials such as Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) using double RAS blockade strongly advises against blocking RAS at multiple levels [14,15,16,17]. Furthermore, the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) also demonstrated that dual RAS blockade was not beneficial compared to monotherapy with an ACE inhibitor (ACEi) or an AT1R blocker (ARB) in preventing serious outcomes in patients with known vascular disease or diabetes with end-organ damage [18,19,20].…”

The Influence of ACE Inhibition on C1-Inhibitor: A Biomarker for ACE Inhibitor-Induced Angioedema?

“…They inhibit the conversion of angiotensin I into angiotensin II and are expected to prevent cardiovascular, cerebrovascular, and renal complications associated with persistent high blood pressure as well as deterioration of heart failure [1, 2]. …”